Abstract：
BACKGROUND: Glucocorticoids (GC) are the most commonly used anti-inflammatory drugs in dermatology. The actions of GCs are mediated by the glucocorticoid receptor (GR). Alternative splicing of GR mRNA gives rise to different isoforms, GRα and GRβ being the most important. GRβ antagonizes the activity of GRα and its up-regulation has been associated with glucocorticoid insensitivity in several non-cutaneous inflammatory diseases.
METHODS: Using immunohistochemical stainings, we analyzed the expression of GRα and GRβ in lesional skin samples of patients with atopic dermatitis, lichen ruber planus, eczema nummulare and lichen simplex chronicus. We also conducted a study of 13 severe atopic patients to investigate the effect of prednisolone treatment on the expression of GR isoforms using quantitative PCR, western blot and immunohistochemical analysis.
RESULTS: GRα and GRβ were expressed in atopic dermatitis, lichen ruber planus, eczema nummulare and lichen simplex chronicus. Our novel finding was that GRβ is abundant in keratinocytes and cutaneous neutrophils. Nuclear staining of both GRα and GRβ was strongest in keratinocytes of patients with lichen ruber planus, whereas the least nuclear positivity was detected in keratinocytes of patients with atopic dermatitis. In severe atopic dermatitis GRα and GRβ were expressed in both peripheral blood mononuclear cells and the skin. The expression of GRα and GRβ varied during prednisolone therapy but the changes were not related to treatment response or GC insensitivity.
CONCLUSIONS: GRα and GRβ are expressed in inflammatory dermatoses. In severe atopic dermatitis the increased expression of GRβ mRNA is not connected to insensitivity against prednisolone treatment.
METHODS: Using immunohistochemical stainings, we analyzed the expression of GRα and GRβ in lesional skin samples of patients with atopic dermatitis, lichen ruber planus, eczema nummulare and lichen simplex chronicus. We also conducted a study of 13 severe atopic patients to investigate the effect of prednisolone treatment on the expression of GR isoforms using quantitative PCR, western blot and immunohistochemical analysis.
RESULTS: GRα and GRβ were expressed in atopic dermatitis, lichen ruber planus, eczema nummulare and lichen simplex chronicus. Our novel finding was that GRβ is abundant in keratinocytes and cutaneous neutrophils. Nuclear staining of both GRα and GRβ was strongest in keratinocytes of patients with lichen ruber planus, whereas the least nuclear positivity was detected in keratinocytes of patients with atopic dermatitis. In severe atopic dermatitis GRα and GRβ were expressed in both peripheral blood mononuclear cells and the skin. The expression of GRα and GRβ varied during prednisolone therapy but the changes were not related to treatment response or GC insensitivity.
CONCLUSIONS: GRα and GRβ are expressed in inflammatory dermatoses. In severe atopic dermatitis the increased expression of GRβ mRNA is not connected to insensitivity against prednisolone treatment.
摘要：
背景：糖皮质激素（GC）是皮肤病学中最常用的抗炎药。GCs的作用由糖皮质激素受体(GR)介导。GRmRNA的选择性剪接产生不同的亚型，Grα和Grβ是最重要的。在几种非皮肤炎症性疾病中，GRβ拮抗GRα的活性，其上调与糖皮质激素不敏感有关。
方法：使用免疫组织化学染色，我们分析了特应性皮炎患者皮损样本中GRα和GRβ的表达，扁平苔藓，湿疹和慢性单纯性苔藓。我们还对13例重度特应性患者进行了一项研究，以使用定量PCR研究泼尼松龙治疗对GR亚型表达的影响。蛋白质印迹和免疫组织化学分析。
结果：在特应性皮炎中表达GRα和GRβ，扁平苔藓，湿疹和慢性单纯性苔藓。我们的新发现是GRβ在角质形成细胞和皮肤中性粒细胞中含量丰富。在扁平苔藓患者的角质形成细胞中，GRα和GRβ的核染色最强，而特应性皮炎患者的角质形成细胞中检测到的核阳性最少。在严重的特应性皮炎中，外周血单核细胞和皮肤中均表达GRα和GRβ。在泼尼松龙治疗期间，GRα和GRβ的表达发生变化，但变化与治疗反应或GC不敏感无关。
结论：GRα和GRβ在炎症性皮肤病中表达。在严重的特应性皮炎中，GRβmRNA表达的增加与对泼尼松龙治疗的不敏感性无关。
方法：使用免疫组织化学染色，我们分析了特应性皮炎患者皮损样本中GRα和GRβ的表达，扁平苔藓，湿疹和慢性单纯性苔藓。我们还对13例重度特应性患者进行了一项研究，以使用定量PCR研究泼尼松龙治疗对GR亚型表达的影响。蛋白质印迹和免疫组织化学分析。
结果：在特应性皮炎中表达GRα和GRβ，扁平苔藓，湿疹和慢性单纯性苔藓。我们的新发现是GRβ在角质形成细胞和皮肤中性粒细胞中含量丰富。在扁平苔藓患者的角质形成细胞中，GRα和GRβ的核染色最强，而特应性皮炎患者的角质形成细胞中检测到的核阳性最少。在严重的特应性皮炎中，外周血单核细胞和皮肤中均表达GRα和GRβ。在泼尼松龙治疗期间，GRα和GRβ的表达发生变化，但变化与治疗反应或GC不敏感无关。
结论：GRα和GRβ在炎症性皮肤病中表达。在严重的特应性皮炎中，GRβmRNA表达的增加与对泼尼松龙治疗的不敏感性无关。
